The factors controlling collagenolytic activity in tumors and the mechanism associated with the destruction of the connective tissue barriers in the host is still poorly understood. We are investigating the interrelationship between different tissue components associated with collagenase production and activity by tumor and host tissue. Our preliminary studies using rabbit V2 carcinoma suggest that the presence of collagenase activity in neoplasm depends on the site of tumor initiation and is influenced by a second tumor in the same animal. We will search for the local or humoral factors manipulating this relationship and for biochemical factors, inhibitors and stimulators which may be responsible for regulating this enzyme activity.